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Bone Marrow Protocol applies to acute leukemias, myelodysplastic syndromes, myeloproliferative disorders, chronic lymphoproliferative disorders, malignant lymphomas, plasma cell dyscrasias, histiocytic and dendritic cell neoplasms and mastocytosis. Protocol revision date: January 2004 No AJCC/UICC staging system Procedures • Blood Film • Aspirate, Cell Block • Trephine Biopsy, Touch Imprint Authors LoAnn C. Peterson, MD Department of Pathology, Northwestern Memorial Hospital, Chicago, Illinois Steven J. Agosti, MD James A. Haley VA Hospital, University of South Florida, Tampa, Florida James Hoyer, MD Hematopathology, Mayo Clinic, Rochester, Minnesota For the Members of the Hematology and Clinical Microscopy Resource Committee and the Cancer Committee, College of American Pathologists

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Page 1: BONE MARROW - meditest.pl€¦ · Web viewBone Marrow. Protocol applies to acute leukemias, myelodysplastic syndromes, myeloproliferative disorders, chronic lymphoproliferative disorders,

Bone MarrowProtocol applies to acute leukemias, myelodysplastic syndromes, myeloproliferative disorders, chronic lymphoproliferative disorders, malignant lymphomas, plasma cell dyscrasias, histiocytic and dendritic cell neoplasms and mastocytosis.

Protocol revision date: January 2004No AJCC/UICC staging system

Procedures• Blood Film• Aspirate, Cell Block • Trephine Biopsy, Touch Imprint

AuthorsLoAnn C. Peterson, MD

Department of Pathology, Northwestern Memorial Hospital, Chicago, IllinoisSteven J. Agosti, MD

James A. Haley VA Hospital, University of South Florida, Tampa, FloridaJames Hoyer, MD

Hematopathology, Mayo Clinic, Rochester, MinnesotaFor the Members of the Hematology and Clinical Microscopy Resource Committee and the Cancer Committee, College of American Pathologists

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Bone Marrow • Hematologic System CAP Approved

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CAP Approved Hematologic System • Bone Marrow

Surgical Pathology Cancer Case Summary (Checklist)Protocol revision date: January 2004

Applies to hematopoietic and lymphoid disordersof the bone marrow only

No AJCC/UICC staging system

BONE MARROW: Blood Film, Aspirate, Cell Block, Trephine Biopsy, Touch Imprint

Patient name:Hematopathology/Surgical pathology number:

Note: Check 1 response unless otherwise indicated.

MACROSCOPIC

Specimen Type___ Aspirate___ Biopsy___ Both aspirate and biopsy___ Blood film___ Cell block (clot section)___ Not specified

*Biopsy Site*___ Not applicable*___ Right posterior iliac crest*___ Left posterior iliac crest*___ Other (specify): ___________________________*___ Not specified

*Aspirate Site*___ Not applicable*___ Right posterior iliac crest*___ Left posterior iliac crest*___ Sternum*___ Other (specify): ___________________________*___ Not specified

* Data elements with asterisks are not required for accreditation purposes for the Commission on Cancer. These elements may be clinically important, but are not yet validated or regularly used in patient management. Alternatively, the necessary data may not be available to the pathologist at the time of pathologic assessment of this specimen.

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Bone Marrow • Hematologic System CAP Approved

Adequacy of Specimen___ Satisfactory___ Limited ___ Unsatisfactory

Phenotyping___ Performed, see separate report___ Performed (specify method and results): _________________________________ Not performed

Cytogenetics___ Performed (see separate report)___ Performed (specify results): ___________________________________ Not performed

WHO Classification (check all that apply)

Chronic Myeloproliferative Diseases___ Chronic myelogenous leukemia___ Chronic neutrophilic leukemia ___ Chronic eosinophilic leukemia/hypereosinophilic syndrome___ Polycythemia vera___ Chronic idiopathic myelofibrosis___ Essential thrombocythemia ___ Myeloproliferative disease, unclassifiable

Myelodysplastic/Myeloproliferative Diseases___ Chronic myelomonocytic leukemia ___ Atypical chronic myeloid leukemia ___ Juvenile myelomonocytic leukemia___ Myelodysplastic/myeloproliferative disease, unclassifiable

Myelodysplastic Syndromes ___ Refractory anemia___ Refractory anemia with ringed sideroblasts___ Refractory cytopenia with multilineage dysplasia___ Refractory cytopenia with multilineage dysplasia and ringed sideroblasts___ Refractory anemia with excess blasts (RAEB)

___ RAEB-1___ RAEB-2

___ Myelodysplastic syndrome, unclassifiable___ Myelodysplastic syndrome associated with isolated del(5q)

* Data elements with asterisks are not required for accreditation purposes forthe Commission on Cancer. These elements may be clinically important,

but are not yet validated or regularly used in patient management.Alternatively, the necessary data may not be available to the pathologist

at the time of pathologic assessment of this specimen.

4

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CAP Approved Hematologic System • Bone Marrow

Acute Myeloid Leukemias (AMLs)___ Acute myeloid leukemia with recurrent genetic abnormalities

___ AML with t(8;21)(q22;q22)___ AML with abnormal bone marrow eosinophils inv(16) or t(16;16) or t(16;16)

(p13;q22);CBF/MYH11)___ Acute promyelocytic leukemia t(15;17)(q22;q12) and variants___ AML with 11q23 (MLL) abnormality

___ Acute myeloid leukemia with multilineage dysplasia___ Following a myelodysplastic syndrome or myelodysplastic

syndrome/myeloproliferative disorder___ Without antecedent myelodysplastic syndrome

___ Acute myeloid leukemia and myelodysplastic syndromes, therapy-related___ Alkylating agent-related ___ Topoisomerase type II inhibitor-related (some may be lymphoid) ___ Other types (specify): _____________________________

___ Acute myeloid leukemia not otherwise categorized___ AML minimally differentiated ___ AML without maturation ___ AML with maturation ___ Acute myelomonocytic leukemia ___ Acute monoblastic and monocytic leukemia ___ Acute erythroid leukemia ___ Acute megakaryoblastic leukemia ___ Acute basophilic leukemia ___ Acute panmyelosis with myelofibrosis ___ Myeloid sarcoma

___ Acute leukemia of ambiguous lineage___ Undifferentiated acute leukemia___ Bilineal acute leukemia___ Biphenotypic acute leukemia

Precursor B-cell and T-cell Neoplasms___ Precursor B lymphoblastic leukemia/lymphoblastic lymphoma ___ Precursor T lymphoblastic leukemia/lymphoblastic lymphoma

* Data elements with asterisks are not required for accreditation purposes for the Commission on Cancer. These elements may be clinically important, but are not yet validated or regularly used in patient management. Alternatively, the necessary data may not be available to the pathologist at the time of pathologic assessment of this specimen.

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Bone Marrow • Hematologic System CAP Approved

Mature B-cell Neoplasms___ Chronic lymphocytic leukemia/small lymphocytic lymphoma ___ B-cell prolymphocytic leukemia ___ Lymphoplasmacytic lymphoma___ Splenic marginal zone lymphoma___ Hairy cell leukemia___ Plasma cell myeloma___ Monoclonal gammopathy of undetermined significance (MGUS)___ Solitary plasmacytoma of bone___ Extraosseus plasmacytoma___ Primary amyloidosis___ Heavy chain disease___ Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue

(MALT-lymphoma)___ Nodal marginal zone B-cell lymphoma ___ Follicular lymphoma

___ Grade 1___ Grade 2___ Grade 3

___ Mantle cell lymphoma___ Diffuse large B-cell lymphoma___ Mediastinal (thymic) large B-cell lymphoma___ Primary effusion lymphoma___ Burkitt lymphoma / leukemia

B-cell Proliferations of Uncertain Malignant Potential___ Lymphomatoid granulomatosis___ Post-transplant lymphoproliferative disorder, polymorphic

* Data elements with asterisks are not required for accreditation purposes forthe Commission on Cancer. These elements may be clinically important,

but are not yet validated or regularly used in patient management.Alternatively, the necessary data may not be available to the pathologist

at the time of pathologic assessment of this specimen.

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CAP Approved Hematologic System • Bone Marrow

Mature T-cell and NK-cell NeoplasmsLeukemic / Disseminated___ T-cell prolymphocytic leukemia ___ T-cell large granular lymphocytic leukemia ___ Aggressive NK-cell leukemia___ Adult T-cell leukemia/lymphomaCutaneous___ Mycosis fungoides___ Sézary syndrome___ Primary cutaneous anaplastic large cell lymphoma___ Lymphomatoid papulosisOther Extranodal___ Extranodal NK/T-cell lymphoma, nasal-type___ Enteropathy-type T-cell lymphoma___ Hepatosplenic T-cell lymphoma___ Subcutaneous panniculitis-like T-cell lymphoma Nodal___ Angioimmunoblastic T-cell lymphoma___ Peripheral T-cell lymphoma, unspecified___ Anaplastic large cell lymphoma

Neoplasm of Uncertain Lineage and Stage of Differentiation___ Blastic NK-cell lymphoma

Hodgkin Lymphoma___ Nodular lymphocyte predominant Hodgkin lymphoma ___ Classical Hodgkin lymphoma

___ Nodular sclerosis classical Hodgkin lymphoma ___ Lymphocyte-rich classical Hodgkin lymphoma___ Mixed cellularity classical Hodgkin lymphoma ___ Lymphocyte-depleted classical Hodgkin lymphoma

Histiocytic and Dendritic-cell Neoplasms___ Histiocytic sarcoma___ Langerhans cell histiocytosis ___ Langerhans cell sarcoma___ Interdigitating dendritic cell sarcoma / tumor___ Follicular dendritic cell sarcoma / tumor___ Dendritic cell sarcoma, not otherwise specified

* Data elements with asterisks are not required for accreditation purposes for the Commission on Cancer. These elements may be clinically important, but are not yet validated or regularly used in patient management. Alternatively, the necessary data may not be available to the pathologist at the time of pathologic assessment of this specimen.

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Bone Marrow • Hematologic System CAP Approved

Mastocytosis___ Indolent systemic mastocytosis___ Systemic mastocytosis with associated clonal, hematologic non-mast-cell lineage

disease___ Aggressive systemic mastocytosis___ Mast cell leukemia___ Mast cell sarcoma

Other___ Malignant neoplasm, type cannot be determined

*Additional Pathologic Findings*Specify: ____________________________________

*Comment(s)

* Data elements with asterisks are not required for accreditation purposes forthe Commission on Cancer. These elements may be clinically important,

but are not yet validated or regularly used in patient management.Alternatively, the necessary data may not be available to the pathologist

at the time of pathologic assessment of this specimen.

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For Information Only Hematologic System • Bone Marrow

Background DocumentationProtocol revision date: January 2004

I. Blood Film, Aspirate, Cell Block, Trephine Biopsy, Touch ImprintA. Clinical Information

1. Patient identificationa. Nameb. Identification numberc. Age (birth date)d. Sex

2. Responsible physician(s)3. Date of procedure4. Other clinical information

a. Relevant history and physical findings (eg, prior diagnosis; prior therapy, including transplantation; physical findings; symptoms; indication for biopsy)

b. Relevant laboratory and radiological data (eg, peripheral blood studies, serum protein analyses, radiographic data, imaging studies)

c. Procedure (eg, aspirate, trephine biopsy)d. Anatomic site(s) of specimen(s) (eg, left and/or right posterior iliac crest)

B. Macroscopic Examination1. Specimen(s) (Note A)

a. Blood(1) fluid specimen (anticoagulated)(2) slides

i. numberii. unstained/stained (specify stain)

b. Aspirate(1) fluid specimen volume(2) slides

i. numberii. unstained/stained (specify stain)

c. Touch preparations(1) number(2) unstained/stained (specify stain)

d. Trephine biopsy(1) unfixed/fixed (specify fixative)(2) size (eg, number of pieces, aggregate length)

e. Other (eg, cell block of particle concentrate)2. Special studies (eg, flow cytometry immunophenotyping, cytogenetic analysis,

molecular genetic analysis)C. Microscopic Examination

1. Blooda. Quantitative cellular data

(1) differential counts (Note B)b. Morphologic cellular data (details of description will depend on morphologic

findings and indication for biopsy)(1) normal cells

i. red blood cellsii. leukocytesiii. platelets

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Bone Marrow • Hematologic System For Information Only

(2) abnormal findings, if presenti. morphologic abnormalities (eg, oval macrocytes, schistocytes,

pseudo-Pelger Hüet neutrophils, giant platelets)ii. abnormal cell types (eg, blasts, micromegakaryocytes)iii. other (eg, microorganisms)

2. Bone marrow aspirate smear(s) and/or touch preparation(s)a. Adequacy of specimen (if unsatisfactory for evaluation, specify reason, eg,

absence of bone marrow elements) b. Quantitative cellular data

(1) differential counts (Note B) (see reference for ranges1)(2) megakaryocytes (Note C)

c. Morphologic cellular data (details of description will depend on morphologic findings and indication for biopsy)(1) normal cells

i. erythroid precursorsii. myeloid cellsiii. megakaryocytesiv. lymphocytesv. others

(2) abnormal findings, if presenti. morphologic abnormalities (eg, megaloblastic hematopoiesis,

dysplasia) ii. abnormal or malignant cells (eg, blasts, lymphoma cells, myeloma

cells, tumor cells)iii. other (eg, fungal organisms)

3. Trephine biopsy and/or cell blocka. Adequacy of specimen (if unsatisfactory for evaluation, specify reason)b. Quantitative cellular data

(1) cellularity and cell composition(2) megakaryocyte numbers

c. Morphologic cellular data (details of description will depend on morphologic findings and indication for biopsy)(1) normal cells

i. erythroid precursorsii. myeloid cellsiii. lymphocytesiv. megakaryocytesv. others

(2) abnormal findings, if present (it is often important to quantify the abnormalities, eg, percent involvement by lymphoma)i. morphologic abnormalities (eg, dysplastic megakaryocytes)ii. abnormal or malignant cells (eg, foci of blasts, lymphoma, myeloma,

metastatic tumor)iii. other (eg, fibrosis, necrosis, granulomata, bony abnormalities)

4. Assessment of iron stores and sideroblastic iron, if performed5. Results of cytochemical stains, if performed (Note D)6. Results of histochemical stains, if performed (eg, reticulin stain, stains for

organisms)7. Results of immunohistochemical reactions, if performed (Note E)

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For Information Only Hematologic System • Bone Marrow

8. Results/status of special studies, if performeda. Immunophenotyping by flow cytometry (Note E)b. Cytogenetic analysis (Note F)c. Molecular analysis (Note G)

9. Diagnostic assessmenta. Diagnosis and classification of disease process with integration of results

from blood, aspirate, and trephine biopsy specimens, as well as special studies (Note H)

10. Commentsa. Correlation with previous bone marrow biopsies (Note I)b. Correlation with other specimens, as appropriatec. Correlation with clinical information, as appropriated. Ancillary studies referred to reference laboratory (Note J)

Explanatory Notes

A. Macroscopic Examination of SpecimenNot all specimen components will be present in an individual case.

B. Quantitative Cellular DataDifferential counts, including the number of cells counted, that are utilized in the evaluation of the specimen should be documented in the report. If estimates are used, these should be documented in the report.

C. Bone Marrow AspirateSince the trephine biopsy usually provides a more accurate assessment of megakaryocyte numbers than the aspirate alone, both should be used, if possible, to quantify megakaryocytes.

D. Cytochemical StainsThe most frequently utilized cytochemical stains for the evaluation of acute leukemias include myeloperoxidase, Sudan black B, non-specific esterase, and periodic acid-Schiff (PAS). Cytochemical stains for acid phosphatase with and without tartrate (TRAP) are often performed to aid in the diagnosis of hairy cell leukemia.

E. Immunophenotyping (Including Immunohistochemistry and/or Flow Cytometry)Immunophenotypic analysis is essential to precisely diagnose and classify many of the hematologic malignancies.2 For example, immunophenotyping is used in the diagnosis of acute leukemias to determine lineage, especially in acute lymphoblastic leukemias and in acute myeloid leukemias (AMLs) that are negative by cytochemical stains for myeloperoxidase (eg, AML minimally differentiated). Evaluation of additional markers in acute leukemia aids in further subclassification (B versus T lineage in acute lymphoblastic leukemias, megakaryocyte lineage of blasts in AML, etc).

Immunophenotyping is also integral to the diagnosis of the chronic lymphoproliferative disorders, such as chronic lymphocytic leukemia, to determine B- or T-cell lineage, test for presence of monotypic immunoglobulin light-chain restriction, and to evaluate for other markers, such as CD5, CD23, and CD103, to aid in categorization of the various disorders. Similarly, work-up of the bone marrow for lymphoma and plasma cell malignancies is aided by immunophenotyping. Immunophenotypic studies are not only

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Bone Marrow • Hematologic System For Information Only

useful for initial diagnosis, but may also be utilized as an adjunct to morphology in determining the presence and extent of bone marrow involvement at the time of staging of lymphomas or following therapy for both leukemias and lymphomas, especially if the phenotype has been previously determined. Immunophenotyping may also be necessary to document antigen expression when immunotherapy, such as anti-CD20, anti-CD33, or anti-CD53, is being considered.

F. Cytogenetic AnalysisCytogenetic analysis is an integral part of the work up and classification of many hematologic malignancies.3 For example, the World Health Organization (WHO) classification for hematologic malignancies (Table 1) incorporates several specific cytogenetic abnormalities into the classification scheme for AMLs.4 The t(15;17) is diagnostic of acute promyelocytic leukemia. Cytogenetic analysis not only aids in the diagnosis and classification of the acute leukemias, but also gives important prognostic information. For example, AMLs associated with some specific translocations, such as t(8;21) and inv(16), occur primarily in younger individuals and are usually accompanied by a good response to therapy and a favorable prognosis. In contrast, AML with multilineage dysplasia is often associated with chromosomal deletions; for example, -7/del(7q), -5/del(5q), occurs more frequently in older individuals and is associated with an unfavorable response to therapy. Among the myeloproliferative disorders, identification of the t(9;22) is essential to confirm a morphologic diagnosis of chronic myelogenous leukemia and separate it from other myeloproliferative disorders.

Detection of cytogenetic alterations in the myelodysplastic syndromes, usually loss of chromosomal material, may also aid the diagnosis and give prognostic information. In addition, cytogenetic studies are used increasingly in the chronic lymphoid leukemias and non-Hodgkin lymphomas primarily to aid in classification but also to obtain prognostic information. Cytogenetic analysis is not only useful at diagnosis but also has utility in evaluating bone marrow after therapy for residual disease. If these results are not available at the time of the bone marrow report, an addendum could be issued when they become available.

G. Molecular AnalysisMolecular analyses are being performed increasingly to evaluate for the presence of genetic abnormalities in all types of hematologic malignancies.5 As with cytogenetic analysis, the detection of several specific genetic alterations gives both diagnostic and prognostic information and can also be used to aid in the detection of minimal residual disease. The most common molecular techniques available at the present time include Southern blot hybridization, polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH). Currently, molecular analysis is most helpful in assessing for clonality and detecting chromosomal translocations, but its role will undoubtedly increase in the future. If these results are not available at the time of the bone marrow report, an addendum could be issued when they become available.

H. Disease ClassificationThe Protocol recommends the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues (Table 1).4 Variants and subtypes of lesions most applicable to bone marrow biopsies are shown in Tables 2 through 6.

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For Information Only Hematologic System • Bone Marrow

I. Previous BiopsyWhen bone marrow biopsies are performed following an initial diagnostic biopsy, comparison of the current biopsy with the prior biopsy findings, if possible and relevant, should be reported.

J. Referred Ancillary StudiesIf ancillary studies are referred to another laboratory, it is suggested that the date of the referral and the name of the reference laboratory be included in the report. If the results are not included in the initial bone marrow report, the status and location of referral laboratory results should be given.

Table 1. World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues

Chronic myeloproliferative diseasesChronic myelogenous leukemia, (Philadelphia chromosome t(9;22)(q34;q11),

BCR/ABL positive)Chronic neutrophilic leukemia Chronic eosinophilic leukemia (and the hypereosinophilic syndrome) Polycythemia veraChronic idiopathic myelofibrosis (with extramedullary hematopoiesis)Essential thrombocythemia Myeloproliferative disease, unclassifiable

Myelodysplastic/myeloproliferative diseases Chronic myelomonocytic leukemia Atypical chronic myeloid leukemia Juvenile myelomonocytic leukemiaMyelodysplastic/myeloproliferative disease, unclassifiable

Myelodysplastic syndromes Refractory anemiaRefractory anemia with ringed sideroblastsRefractory cytopenia with multilineage dysplasiaRefractory cytopenia with multilineage dysplasia and ringed sideroblastsRefractory anemia with excess blasts (RAEB)

RAEB-1RAEB-2

Myelodysplastic syndrome, unclassifiableMyelodysplastic syndrome associated with isolated del(5q) chromosome

abnormalityAcute myeloid leukemias (AML)

Acute myeloid leukemia with recurrent genetic abnormalities AML with t(8;21)(q22;q22); (AML1/ETO)AML with abnormal bone marrow eosinophils (inv(16)(p13q22) or t(16;16)

(p13;q22);CBF/MYH11)Acute promyelocytic leukemia (AML) with t(15;17)(q22;q11-12)

PML/RAR) and variantsAML with 11q23 (MLL) abnormalities

Acute myeloid leukemia with multilineage dysplasiaFollowing a myelodysplastic syndrome or myelodysplastic

syndrome/myeloproliferative disorderWithout antecedent myelodysplastic syndrome

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Bone Marrow • Hematologic System For Information Only

Acute myeloid leukemia and myelodysplastic syndromes, therapy relatedAlkylating agent-related Topoisomerase type II inhibitor-related (some may be lymphoid) Other types

Acute myeloid leukemia not otherwise categorizedAML, minimally differentiated AML without maturation AML with maturation Acute myelomonocytic leukemia Acute monoblastic and monocytic leukemia Acute erythroid leukemia Acute megakaryoblastic leukemia Acute basophilic leukemia Acute panmyelosis with myelofibrosis Myeloid sarcoma

Acute leukemia of ambiguous lineageUndifferentiated acute leukemiaBilineal acute leukemiaBiphenotypic acute leukemia

Precursor B-cell and T-cell neoplasmsPrecursor B lymphoblastic leukemia/lymphoblastic lymphoma

(precursor B-cell acute lymphoblastic leukemia)Precursor T lymphoblastic leukemia/lymphoblastic lymphoma

(precursor T-cell acute lymphoblastic leukemia)Mature B-cell neoplasms

Chronic lymphocytic leukemia/small lymphocytic lymphoma B-cell prolymphocytic leukemia Lymphoplasmacytic lymphomaSplenic marginal zone lymphomaHairy cell leukemiaPlasma cell myelomaMonoclonal gammopathy of undetermined significance (MGUS)Solitary plasmacytoma of boneExtraosseus plasmacytomaPrimary amyloidosisHeavy chain diseasesExtranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid

tissue (MALT lymphoma)Nodal marginal zone B-cell lymphoma Follicular lymphoma

Grade 1Grade 2Grade 3

Mantle cell lymphomaDiffuse large B-cell lymphomaMediastinal (thymic) large B-cell lymphomaPrimary effusion lymphomaBurkitt lymphoma / leukemia

B-cell proliferations of uncertain malignant potentialLymphomatoid granulomatosisPost-transplant lymphoproliferative disorder, polymorphic

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For Information Only Hematologic System • Bone Marrow

Mature T-cell and natural killer (NK)-cell neoplasmsLeukemic / disseminated

T-cell prolymphocytic leukemia T-cell large granular lymphocytic leukemia Aggressive NK-cell leukemiaAdult T-cell leukemia/lymphoma

CutaneousMycosis fungoidesSézary syndromePrimary cutaneous anaplastic large cell lymphomaLymphomatoid papulosis

Other extranodalExtranodal NK/T-cell lymphoma, nasal-typeEnteropathy-type T-cell lymphomaHepatosplenic T-cell lymphomaSubcutaneous panniculitis-like T-cell lymphoma

NodalAngioimmunoblastic T-cell lymphomaPeripheral T-cell lymphoma, unspecifiedAnaplastic large cell lymphoma

Neoplasm of uncertain lineage and stage of differentiationBlastic NK-cell lymphoma

Hodgkin lymphomaNodular lymphocyte predominant Hodgkin lymphoma Classical Hodgkin lymphoma

Nodular sclerosis classical Hodgkin lymphoma Lymphocyte-rich classical Hodgkin lymphoma, Mixed cellularity classical Hodgkin lymphoma Lymphocyte-depleted classical Hodgkin lymphoma

Histiocytic and dendritic-cell neoplasmsHistiocytic sarcomaLangerhans cell histiocytosis Langerhans cell sarcomaInterdigitating dendritic cell sarcoma / tumorFollicular dendritic cell sarcoma / tumorDendritic cell sarcoma, not otherwise specified

MastocytosisCutaneous mastocytosisIndolent systemic mastocytosisSystemic mastocytosis with associated clonal, hematologic nonmast-cell lineage

diseaseAggressive systemic mastocytosisMast cell leukemiaMast cell sarcomaExtracutaneous mastocytoma

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Bone Marrow • Hematologic System For Information Only

Table 2. Genetic Subgroups of Precursor B-Lymphoblastic Leukemia/Lymphoblastic Lymphoma

Genetic Abnormalities Prognosis t(9;22)(q34;q11.2); BCR/ABL Unfavorablet(4;11)(q21;23); AF4/MLL Unfavorablet(1;19)(q23;p13.3) PBX/E2A Unfavorable but varies with therapeutic regiment(12;21)(p12;q22) TEL/AML1 FavorableHyperdiploid > 50 FavorableHypodiploidy Unfavorable

Table 3. Diffuse Large B-Cell Lymphoma, Morphologic Variants and Subtypes

Morphologic variantsCentroblastic Immunoblastic T-cell/histiocyte-rich Anaplastic

Other variants / subtypesPlasmablasticDiffuse large B-cell lymphoma with expression of full-length ALK

Table 4. Burkitt Lymphoma, Morphologic Variants and Subtypes

Burkitt lymphoma, morphologic variantsClassicalVariants

Burkitt lymphoma with plasmacytoid differentiationAtypical Burkitt/Burkitt-like

Burkitt lymphoma, subtypes (clinical and genetic) Endemic Sporadic Immunodeficiency-associated

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For Information Only Hematologic System • Bone Marrow

Table 5. Plasma Cell Neoplasms: Subtypes and Variants

Plasma cell myeloma variantsNon-secretory myelomaIndolent myeloma Smoldering myeloma Plasma cell leukemia

PlasmacytomaSolitary plasmacytoma of bone Extramedullary plasmacytoma

Immunoglobulin deposition diseasesPrimary amyloidosisSystemic light and heavy chain deposition diseases

Osteosclerotic myeloma (POEMS) syndromeHeavy chain diseases (HCD)

Gamma HCDMu HCDAlpha HCD

Table 6. Categories of Post-Transplant Lymphoproliferative Diseases (PTLD)

Early lesionsReactive plasmacytic hyperplasiaInfectious mononucleosis-like

Polymorphic PTLDMonomorphic (classify according to lymphoma classification)

B-cell neoplasms Diffuse large B-cell lymphoma (immunoblastic, centroblastic, anaplastic)

Burkitt/Burkitt-like lymphomaPlasma cell myelomaPlasmacytoma-like lesions

T-cell lymphomas Peripheral T-cell lymphoma, not otherwise specified Other types

Hodgkin lymphoma and Hodgkin lymphoma-like PTLD Hodgkin lymphoma

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References1. Bain BJ. The bone marrow aspirate of healthy subjects. Br J Haematol.

1996;94:206-209.2. Jennings CD, Foon KA. Review: recent advances in flow cytometry application to

the diagnosis of hematologic malignancy. Blood. 1997;90:2863-2892.3. LeBeau MM. Role of Cytogenetics in the Diagnosis and Classification of

Hematopoietic Neoplasms. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:391-418.

4. Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001.

5. Bagg A, Kallakury BVS. Molecular pathology of leukemia and lymphoma. Am J Clin Pathol. 1999;112(Suppl 1):S76-S92.

BibliographyBennett JM, Catovsky D, Daniel MT, et al. Criteria for the diagnosis of acute leukemia of

megakaryocytic lineage (M7): a report of the French-American-British Cooperative Group. Ann Intern Med. 1985;103:460-462.

Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982;51:189-199.

Bennett JM, Catovsky D, Daniel MT, et al. Proposed revised criteria for the classification of acute myeloid leukemia: a report of the French-American-British Cooperative Group. An Intern Med. 1985;103:620-625.

Bennett JM, Catovsky D, Daniel MT, et al. The chronic myeloid leukemias: guidelines for distinguishing chronic granulocytic, atypical chronic myeloid, and chronic myelomonocytic leukaemia. Br J Haematol. 1994;87:746-754.

Brunning RD, McKenna RW. Tumors of the Bone Marrow. Third Series, Fascicle 9. Washington, DC: Armed Forces Institute of Pathology; 1994.

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